RT Journal Article
SR Electronic
T1 Ivermectin: A Positive Allosteric Effector of the α7 Neuronal Nicotinic Acetylcholine Receptor
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 283
OP 294
DO 10.1124/mol.53.2.283
VO 53
IS 2
A1 Krause, Ryoko M.
A1 Buisson, Bruno
A1 Bertrand, Sonia
A1 Corringer, Pierre-Jean
A1 Galzi, Jean-Luc
A1 Changeux, Jean-Pierre
A1 Bertrand, Daniel
YR 1998
UL http://molpharm.aspetjournals.org/content/53/2/283.abstract
AB We report that preapplication of ivermectin, in the micromolar range, strongly enhances the subsequent acetylcholine-evoked current of the neuronal chick or human α7 nicotinic acetylcholine receptors reconstituted in Xenopus laevis oocytes and K-28 cells. This potentiation does not result from nonspecific Cl−currents. The concomitant increase in apparent affinity and cooperativity of the dose-response curve suggest that ivermectin acts as a positive allosteric effector. This interpretation is supported by the observation of an increase in efficiency of a partial agonist associated with the potentiation and by the differential effect of ivermectin on mutants within the M2 channel domain. Ivermectin effects reveal a novel allosteric site for pharmacological agents on neuronal α7 nicotinic acetylcholine receptors.